Stress exposure can take a toll on the adjustment of young individuals, including students. The aim of this study was to investigate the impact of burnout and impostor syndrome (IS) on self-esteem and academic performance in medical students. The participants were 331 undergraduate medical students (102 men, 229 women; 89.7% native, 12,1% international; mean age = 21.18, SD = 2.338). The study instruments included the Copenhagen Burnout Inventory for Students (CBI-S), Clance Impostor Phenomenon Scale (CIPS), and Rosenberg’s Self-Esteem Scale, while academic performance (AP) was reported as received GPA (objective AP) and expected GPA (subjective AP). The statistical analysis comprised independent t-tests, MANOVA, ANOVA, and correlational and mediational analyses. The results showed that native students had lower self-esteem and higher scores of personal burnout and IS. Irrespective of cultural differences, women scored higher than men in IS and in personal burnout, while men had higher self-esteem than women. Burnout and IS were correlated with a decrease in self-esteem (adj. R² = 0.531) in the overall sample, whereas in native students, IS was correlated with a difference between subjective and objective self-assessments of AP (adj. R² = 0.027). Burnout and impostor syndrome, despite not directly impacting academic performance, may significantly influence self-esteem, making them a target for preventive or interventional measures.